17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan hydrochloride represented by the following formula (I):
is described in patent document 1. This compound has been demonstrated to be a compound useful as an active ingredient of analgesic, diuretic and antipruritic agents. Patent document 1 specifically discloses the compound together with physiochemical properties thereof.
[Patent document 1]: JP Patent No. 2525552 (Example 68)
During intensive studies on the physical properties of the compound represented by the above formula (I), the present inventors have found that whereas the compound (I) produced according to Example 68 in patent document 1 is amorphous as shown in FIG. 4, compound (I) has crystal polymorphism, i.e., is present as an A-form, B-form or C-form crystal as described later, when produced by a method different from the above method.
Generally, a compound having crystal polymorphism sometimes has physical properties different for each crystal. Particularly in the medicinal field, there are known to be differences in terms of solubility, solution velocity, stability, absorbability, or the like. Thus, it is possible that even use of the same compound provides no desired potency thereof or leads to a potency different from that predicted owing to a difference in crystal form, which causes unforeseen circumstances. For that reason, there is a need for the provision of the compound of consistent quality which can be expected to always have a constant potency.
Thus, when a compound having crystal polymorphism is used as a medicine, it is necessary to stably provide the compound having uniform crystal form in order to ensure the uniform quality and constant potency thereof.
The presence of a crystal of the compound represented by the above formula (I) has previously been quite unknown, and patent document 1 also does not describe or suggest the presence of a crystal or crystal polymorphism thereof.
Accordingly, the present inventors compared an amorphous form of compound (I) prepared according to Example 68 in patent document 1 with a crystal of compound (I) produced by a method different from the above method. As a result, it has been found that whereas the amorphous compound is not consistent in quality after production and has low purity, the crystal has no such problems and is excellent as an active ingredient of medicines or as a preparation for analyzing medicines.